Data from: Modeling stereospecific drug interactions with beta-adrenergic receptor

Beta blockers antagonize βARs, reducing heart rate and lowering vascular tone. We developed a new Rosetta structural modeling protocol to create state-specific models of β1AR and investigated its atomistic-scale interactions with beta-blocker stereoisomers: d- and l-sotalol, as well as R- and S-propranolol.

Our combined molecular dynamics (MD) simulations and docking protocol effectively captured the differences in stereoisomer specificity in binding to β1AR. Binding energetics results favored l-sotalol and S-propranolol, consistent with experimental findings showing d-sotalol has significantly lower affinity for beta-adrenergic receptors than l-sotalol. The entropy term was identified as the primary factor driving enantiomer binding specificity, with higher entropy costs for d-sotalol and R-propranolol due to their unfavorable chiral structures.